ArticleProceedings of the National Academy of Sciences of the United States of America2019
Neurokinin-1 receptor is an effective target for treating leukemia by inducing oxidative stress through mitochondrial calcium overload.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
- The C-terminal truncated splicing variant of NK1R negatively modulates substance P-stimulated NK1R signaling.FEBS open bio · 2026Article
- Aprepitant, a Neurokinin-1 Receptor Antagonist, as a Disruptive Drug for the Treatment of Pediatric Cancer.Journal of clinical medicine · 2026Review
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Drug-assisted synthesis of copper nanoparticles and their induction of cuproptosis and necrosis for breast cancer therapy.Journal of Zhejiang University. Science. B · 2025Article
- Targeting metalloptosis in tumor therapy: from molecular mechanisms to application of metal nanoparticles.Molecular cancer · 2025Review
- Nf2/FGFR1/AKT axis directs cranial neural crest-derived skull morphogenesis via collagen synthesis and trafficking.JCI insight · 2025Article
- Tumor Innervation: From Bystander to Emerging Therapeutic Target for Cancer.International journal of molecular sciences · 2025Review
- Unraveling the neuroimmune mechanisms in cancer-induced bone pain: New horizons for therapeutic intervention of the two-phase paradigm.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The role of the enteric nervous system in the pathogenesis of Clostridioides difficile infection.Nature reviews. Gastroenterology & hepatology · 2025Review
- A New Adjuvant Treatment for Glioblastoma Using Aprepitant, Vortioxetine, Roflumilast and Olanzapine: The AVRO Regimen.International journal of molecular sciences · 2025Review
- The neuroscience of cancer: Focus on neuropeptidergic systems.Acta pharmaceutica Sinica. B · 2025Review
- The role of mitochondria-associated ER membranes in disease pathology: protein complex and therapeutic targets.Frontiers in cell and developmental biology · 2025Review
- Homologous-adhering/targeting cell membrane- and cell-mediated delivery systems: a cancer-catch-cancer strategy in cancer therapy.Regenerative biomaterials · 2025Review
- Overcoming amphotericin B resistance inAntimicrobial agents and chemotherapy · 2024Article
- Neurokinin-2 receptor antagonist SR48968 induced necroptosis of myeloid leukemia cells by calcium overload-driven reactive oxygen species accumulation.Genes & diseases · 2024Article
- Advances in the research and application of neurokinin-1 receptor antagonists.Journal of Zhejiang University. Science. B · 2024Review
- Calcium-based biomaterials: Unveiling features and expanding applications in osteosarcoma treatment.Bioactive materials · 2024Review
- The Repurposing of Non-Peptide Neurokinin-1 Receptor Antagonists as Antitumor Drugs: An Urgent Challenge for Aprepitant.International journal of molecular sciences · 2023Review
- Cell-surface photochemistry mediated calcium overload for synergistic tumor therapy.Journal of nanobiotechnology · 2023Article
- Aprepitant inhibits the progression of esophageal squamous cancer by blocking the truncated neurokinin‑1 receptor.Oncology reports · 2023Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substance P (SP) regulates multiple biological processes through its high-affinity neurokinin-1 receptor (NK-1R). While the SP/NK-1R signaling axis is involved in the pathogenesis of solid cancer, the role of this signaling pathway in hematological malignancy remains unknown. Here, we demonstrate that NK-1R expression is markedly elevated in the white blood cells from acute myeloid leukemia patients and a panel of human leukemia cell lines. Blocking NK-1R induces apoptosis in vitro and in vivo via increase of mitochondrial reactive oxygen species. This oxidative stress was triggered by rapid calcium flux from the endoplasmic reticulum into mitochondria and, consequently, impairment of mitochondrial function, a mechanism underlying the cytotoxicity of NK-1R antagonists. Besides anticancer activity, blocking NK-1R produces a potent antinociceptive effect in myeloid leukemia-induced bone pain by alleviating inflammation and inducing apoptosis. These findings thus raise the exciting possibility that the NK-1R antagonists, drugs currently used in the clinic for preventing chemotherapy-induced nausea and vomiting, may provide a therapeutic option for treating human myeloid leukemia.
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